Novel thiazole and oxazole containing cyclic hexapeptides from a waterbloom of the cyanobacterium Microcystis sp.

Eight novel thiazole and oxazole containing cyclic peptides, microcyclamides GL616, GL582, GL614A, GL614B, GL614C, GL546A, GL546B, and GL628, as well as the known microcyclamide A, were isolated from the hydrophylic extract of a Microcystis sp. water-bloom collected in Gilboa reservoir, Valley of Armageddon, Israel. The planar structure of the compounds was determined by homonuclear and inverse-heteronuclear 2D NMR techniques as well as high-resolution mass spectrometry. The absolute configuration of the asymmetric centers of the amino acids was studied using Marfey's method for HPLC following ozonolysis, hydrolysis and derivatization with Marfey's reagent. This is the first example where acidic and modified amino acids are incorporated in this group of ribosomally biosynthesized metabolites.     

New microviridins from a water bloom of the cyanobacterium Microcystis aeruginosa

Three new microviridins namely, SD1684 (1), SD1634 (2), and SD1652 (3), were isolated from the hydrophilic extract of Microcystis aeruginosa. The planar structures of compounds 1-3 were determined by homonuclear and inverse-heteronuclear 2D-NMR techniques as well as by high-resolution mass spectrometry. The absolute configuration of the asymmetric centers was studied using Marfey's method for HPLC. Compounds 1-3 contain l-threo-β-hydroxy aspartic acid as a building block of the peptide chain. This is the first example where microviridins contain non-proteinogenic amino acid in their structure. Compound 2 is a mild serine protease inhibitor.     

Eight novel serine proteases inhibitors from a water bloom of the cyanobacterium Microcystis sp.

Eight new secondary metabolites, micropeptin MM836 (1), micropeptin MM850 (2), micropeptin MM916 (3), micropeptin MM932 (4), micropeptin MM978 (5), anabaenopeptin MM823 (6), anabaenopeptin MM850 (7), and anabaenopeptin MM913 (8), as well as the known anabaenopeptin B (9) were isolated from the hydrophilic extract of the cyanobacterium Microcystis sp. that was collected from a fishpond in Kibbutz Ma’agan Michael, Israel, in September 2006. The structure of the pure natural products was established by spectroscopic methods including 1D and 2D NMR, UV, and MS techniques. The absolute configuration of the chiral centers of the compounds was determined using Marfey’s method. The inhibitory activity of the compounds was determined against the serine proteases, trypsin, chymotrypsin, thrombin and elastase.     

Protease inhibitors from three fishpond water blooms of Microcystis spp.

Four new natural products, micropeptin GH979 (1), microginin GH787 (2), micropeptin HM978 (3), and micropeptin HA983 (4), as well as 10 known protease inhibitors and hepatotoxins, were isolated from the hydrophilic extract of three samples of cyanobacteria (Microcystis spp.) that were collected from fishponds in Kibbutz Giva’at Haim, Kibbutz Hama’apil, and Kibbutz Gan Shmuel. The structures of the pure natural products were elucidated using spectroscopic methods, including UV, 1D and 2D NMR, and MS techniques. The absolute configuration of the chiral centers of the compounds was determined using Marfey’s method. The inhibitory activity of the compounds was determined for the serine proteases: trypsin, chymotrypsin, thrombin and elastase, and the metalloprotease, aminopeptidase N.     

Three novel metabolites from a bloom of the cyanobacterium Microcystis sp.

Three new metabolites, microphycin AL828, microguanidine AL772, and microginin AL584 and three known metabolites, anabaenopeptin F, oscillamide Y, and microcin SF608 were isolated from the extracts of a Microcystis sp. bloom collected in Alonim reservoir, Valley of Armagedon, Israel. The planar structure of the compounds was determined by homonuclear and inverse-heteronuclear 2D-NMR techniques as well as high-resolution mass spectrometry. The absolute configuration of the asymmetric centers of the amino acids was studied using Marfey's method for HPLC.     

Cytotoxic ent-kauranoid derivatives from Isodon rubescens

An extensive study of the diterpenoids produced by the species of Isodon rubescens, has led to the isolation of 12 new ent-kaurane diterpenoids, hebeirubescensins A-L (1-12), and 19 known analogues. Their structures were determined on the basis of spectroscopic analysis. Selected compounds were assayed for their inhibitory ability against human A549, HT-29, and K562 cells. Among them, hebeirubescensins B and C exhibited significant cytotoxicity with IC₅₀ values of <2.0 μM. The structure-activity relationships were discussed.     

Banyasin A and banyasides A and B, three novel modified peptides from a water bloom of the cyanobacterium Nostoc sp.

Three new modified peptides banyasin A, banyaside A and banyaside B were isolated from the hydrophilic extract of a natural bloom of the cyanobacterium Nostoc sp. The planar structure of the new compounds was determined by homonuclear and inverse-heteronuclear 2D NMR techniques as well as high-resolution mass spectrometry. Banyasides A and B, are structurally closely related to the cyanobacteria metabolite, suomilide and to the sponge derived, dysinosins. The absolute configuration of the asymmetric centers was studied using Marfey's method for HPLC. Banyaside A and B were found to be trypsin and thrombin inhibitors.     

Marine bacterial inhibitors from the sponge-derived fungus Aspergillus sp.

Chromatographic separation of a crude extract obtained from the fungus Aspergillus sp., isolated from the Mediterranean sponge Tethya aurantium, yielded a new tryptophan derived alkaloid, 3-((1-hydroxy-3-(2-methylbut-3-en-2-yl)-2-oxoindolin-3-yl)methyl)-1-methyl-3,4-dihydrobenzo[e][1,4]diazepine-2,5-dione (1), and a new meroterpenoid, austalide R (2), together with three known compounds (3–5). The structures of the new compounds were unambiguously elucidated on the basis of extensive one and two-dimensional NMR (¹H, ¹³C, COSY, HMBC, and ROESY) and mass spectral analysis. Interestingly, the compounds exhibited antibacterial activity when tested against a panel of marine bacteria, with 1 selectively inhibiting Vibrio species and 2 showing a broad spectrum of activity. In contrast, no significant activity was observed against terrestrial bacterial strains and the murine cancer cell line L5178Y.     

Two new microcyclamides from a water bloom of the cyanobacterium Microcystis sp.

Two new thiazole-containing cyclic hexapeptides, microcyclamides MZ602 and MZ568, were isolated from the hydrophilic extract of the cyanobacterium Microcystis sp. The structures of the pure natural products were elucidated using spectroscopic methods including UV, 1D and 2D NMR, and MS techniques. The absolute configuration of the chiral centres of the modified cyclic peptides was determined using Marfey’s method for HPLC. The microcyclamides have been evaluated for their cytotoxicity against leukemia cell lines and inhibition of serine proteases.     

Two novel diterpenoids from Isodon rubescens var. lushanensis

Two novel diterpenoids, luanchunins A (1) and B (2), along with their precursor, kamebakaurin (3), had been isolated from the stems and leaves of Isodon rubescens var. lushanensis. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compounds 1 and 2 showed potent cytotoxic activity against HL-60 with IC₅₀ values of 4.81 μM and 3.52 μM, respectively. Plausible pathways for the biosynthesis of 1 and 2 were also postulated.     

An asymmetric ent-kauranoid dimer from Isodon rubescens var. lushanensis

A novel asymmetric ent-kauranoid dimer, lushanrubescensin J (1), was isolated from Isodon rubescens var. lushanensis. Its structure was elucidated by the spectroscopic evidences. The stereochemistry was confirmed by the single crystal X-ray diffraction of its tetraacetate. Compound (1) exhibited potent inhibitory activity against K562 cells with IC₅₀ = 0.93 μg/mL.     

Two novel tricyclic diterpenoids from Isodon rubescens var. taihangensis

Two novel tricyclic diterpenoids rubescensins U (1) and V (2) were isolated from the leaves of Isodon rubescens var. taihangensis. They were elucidated as a 8,15-seco-ent-kauranoid and an ent-abietanoid, respectively, by 1D and 2D NMR spectra, and single crystal X-ray analysis. Compound 1 is the first example of an 8,15-seco-ent-kaurane from the plants genus Isodon. A discussion of their biogenesis is described.     

Novel ent-kaurane dimers from Isodon rubescens var. rubescens

Three novel asymmetric ent-kaurane dimers xindongnins M-O (1-3) were isolated from Isodon rubescens var. rubescens. Their structures were elucidated by spectroscopic methods including 2D NMR analysis. The relative stereochemistry of 1 was determined by single crystal X-ray diffraction, which also confirmed the unique linkage of a single carbon-carbon bond between the two subunits of this dimer. A biogenetic pathway was proposed for the formation of these dimers.     

Further syphonosides from the sea hare Syphonota geographica and the sea-grass Halophila stipulacea

The unusual structural features of syphonoside (1), recently reported from the marine mollusc Syphonota geographica and its prey Halophila stipulacea, stimulated further investigations on the minor secondary metabolites of both organisms. The three novel macrocyclic glycoterpenoids 2-4, structurally related to the main co-occurring metabolite 1, have been isolated and chemically characterized mainly by NMR spectroscopic techniques and degradation methods. Compounds 2 and 3 were found only in the mollusc whereas compound 4 was isolated in trace quantities exclusively from the sea-grass.     

Stereochemical challenges in characterizing nitrogenous spiro-axane sesquiterpenes from the Indo-Pacific sponges Amorphinopsis and Axinyssa

An investigation was conducted to identify the structures and bioactive properties of five compounds isolated from the Halichondrida sponges Amorphinopsis foetida and Axinyssa aplysinoides. All compounds possessed the spiro-axane sesquiterpene core and all were substituted at C-2 with nitrogen containing functionality. The stereochemistry of one known compound has been revised to (2R,5R,10S)-2-formamido-6-axene (3). It exhibited mild selective solid tumor and mild antibacterial activity and was found from Axinyssa. A second known substance whose stereochemistry has also been revised, (2R,5R,10S)-2-isothiocyanato-6-axene (4) plus its undescribed diastereomer (5) were isolated from Amorphinopsis. Both sponges were the source of two new N-phenethyl-2-formamido-6-axene diastereomeric compounds 6 and 7. No solid tumor or antibacterial activity was found for 4-7.     

Arabinofuranose disaccharide analogs as inhibitors of Mycobacterium tuberculosis

Several octyl 5-O-(α-d-arabinofuranosyl)-α-d-arabinofuranoside disaccharide analogs substituted at the 5-position of the non-reducing end sugar were synthesized and tested in vitro against Mycobacterium tuberculosis (M.tb.), Mycobacterium avium complex (MAC) as well as in a cell free assay system for arabinosyltransferase acceptor/inhibitor activity. A few compounds showed interesting inhibitory activity in the cell free assay as well as against the whole microorganism in vitro.     

Caldorin,a new polyketide from the marine cyanobacterium Caldora penicillata

A new polyketide with a cis-fused decalin ring scaffold, caldorin, was isolated from the marine cyanobacterium Caldora penicillata. The gross structure and relative configuration were elucidated by spectroscopic analyses. We also clarified that caldorin is a weak SOAT inhibitor and moderate osteoblast differentiation inhibitor. On the other hand, caldorin did not exhibit cytotoxicity against either HeLa or HL60 cells.     

Liquidambar styraciflua: a renewable source of shikimic acid

An isolation procedure is presented that yields 2.4-3.7% w/w pure shikimic acid from the seeds of Liquidambar styraciflua (Sweetgum). Shikimic acid, the starting material in the commercial synthesis of the antiviral agent oseltamivir and an important intermediate in the biosynthesis of aromatic amino acids in plants, was found by HPLC to be abundant in the granular, aborted seeds (6.5% w/w) while present only in small amounts in the developed, fertile seeds (0.14% w/w). This extraction technique makes L. styraciflua, which is found in 40 states of the continental US, a potential renewable source of this important natural product.     

Cebulactams A1 and A2, new macrolactams isolated from Saccharopolyspora cebuensis, the first obligate marine strain of the genus Saccharopolyspora

The new macrolactams cebulactams A1 and A2 were isolated from an extract of the first obligate marine strain of the genus Saccharopolyspora. Their constitutionally identical structures, each bearing a six-membered cyclic ether as part of the macrocycle, and their relative configurations were elucidated by MS methods and by 1D and 2D NMR techniques.     

Kuroshines A and B,new alkaloids from Zoanthus kuroshio

A chemical investigation of Zoanthus kuroshio has yielded two new alkaloids, kuroshines A (1) and B (2). The compounds possess a densely functionalized ring system on the basis of the zoanthamine frames. The structures of 1 and 2 were elucidated through interpretation of spectroscopic methods, especially 2D NMR techniques (COSY, HMQC, HMBC, and ROESY). The absolute stereochemistry of 1 was further confirmed by an X-ray single crystallographic analysis using a mirror Cu-Kα radiation.